题目：Immune-related adverse events for anti-PD-1 and anti-PD-L1 drugs: systematic review and meta-analysis
To evaluate rates of serious organ specific immunerelated adverse events, general adverse events related to immune activation, and adverse events consistent with musculoskeletal problems for anti-programmed cell death 1 (PD-1) drugs overall and compared with control treatments.
Systematic review and meta-analysis.
Medline, Embase, Cochrane Library, Web of Science, and Scopus searched to 16 March 2017 and combined with data from ClinicalTrials.gov.
Eligible studies included primary clinical trial data on patients with cancer with recurrent or metastatic disease.
Three independent investigators extracted data on adverse events from ClinicalTrials.gov and the published studies. Risk of bias was assessed using
the Cochrane tool by three independent investigators.
13 relevant studies were included; adverse event data were available on ClinicalTrials.gov for eight. Studies compared nivolumab (n=6), pembrolizumab (5), or atezolizumab (2) with chemotherapy (11), targeted drugs (1), or both (1). Serious organ specific immunerelated adverse events were rare, but compared with standard treatment, rates of hypothyroidism (odds ratio 7.56, 95% confidence interval 4.53 to 12.61), pneumonitis (5.37, 2.73 to 10.56), colitis (2.88, 1.30 to 6.37), and hypophysitis (3.38, 1.02 to 11.08) were increased with anti-PD-1 drugs. Of the general adverse events related to immune activation, only
the rate of rash (2.34, 2.73 to 10.56) increased. Incidence of fatigue (32%) and diarrhea (19%) were high but similar to control. Reporting of adverse events consistent with musculoskeletal problems was inconsistent; rates varied but were over 20% in some studies for arthraligia and back pain.
Organ specific immune-related adverse events
are uncommon with anti-PD-1 drugs but the risk
is increased compared with control treatments.
General adverse events related to immune activation
are largely similar. Adverse events consistent with
musculoskeletal problems are inconsistently reported
but adverse events may be common.